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E E Nikolsky - One of the best experts on this subject based on the ideXlab platform.
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metabotropic Gabab receptors mediate Gaba inhibition of acetylcholine release in the rat neuromuscular junction
Journal of Neurochemistry, 2015Co-Authors: A I Malomouzh, Konstantin A Petrov, L F Nurullin, E E NikolskyAbstract:Gamma-aminobutyric acid (Gaba) is an amino acid which acts as a neurotransmitter in the central nervous system. Here, we studied the effects of Gaba on non-quantal, spontaneous, and evoked quantal acetylcholine (ACh) release from motor nerve endings. We found that while the application of 10 μM of Gaba had no effect on spontaneous quantal ACh release, as detected by the frequency of miniature endplate potentials, Gaba reduced the non-quantal ACh release by 57%, as determined by the H-effect value. Finally, the evoked quantal ACh release, estimated by calculating the quantal content of full-sized endplate potentials (EPPs), was reduced by 34%. Gaba's inhibitory effect remained unchanged after pre-incubation with picrotoxin, an ionotropic GabaA receptor blocker, but was attenuated following application of the GabaB receptor blocker CGP 55845, which itself had no effect on ACh release. An inhibitor of phospholipase C, U73122, completely prevented the Gaba-induced decrease in ACh release. Immunofluorescence demonstrated the presence of both subunits of the GabaB receptor (GabaB R1 and GabaB R2) in the neuromuscular junction. These findings suggest that metabotropic GabaB receptors are expressed in the mammalian neuromuscular synapse and their activation results in a phospholipase C-mediated reduction in the intensity of non-quantal and evoked quantal ACh release. We investigated the effect of gamma-aminobutyric acid (Gaba) on neuromuscular transmission. Gaba reduced the non-quantal and evoked quantal release of acetylcholine. These effects are mediated by GabaB receptors and are implemented via phospholipase C (PLC) activation. Our findings suggest that in the mammalian neuromuscular synapse, metabotropic GabaB receptors are expressed and their activation results in a reduction in the intensity of acetylcholine release.
Peter D Lukasiewicz - One of the best experts on this subject based on the ideXlab platform.
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developmental regulation and activity dependent maintenance of Gabaergic presynaptic inhibition onto rod bipolar cell axonal terminals
Neuron, 2013Co-Authors: Timm Schubert, Peter D Lukasiewicz, Mrinalini Hoon, Thomas Euler, Rachel O L WongAbstract:Presynaptic inhibition onto axons regulates neuronal output, but how such inhibitory synapses develop and are maintained in vivo remains unclear. Axon terminals of glutamatergic retinal rod bipolar cells (RBCs) receive GabaA and GabaC receptor-mediated synaptic inhibition. We found that perturbing Gabaergic or glutamatergic neurotransmission does not prevent Gabaergic synaptogenesis onto RBC axons. But, Gaba release is necessary for maintaining axonal Gaba receptors. This activity-dependent process is receptor subtype specific: GabaC receptors are maintained, whereas GabaA receptors containing α1, but not α3, subunits decrease over time in mice with deficient Gaba synthesis. GabaA receptor distribution on RBC axons is unaffected in GabaC receptor knockout mice. Thus, GabaA and GabaC receptor maintenance are regulated separately. Although immature RBCs elevate their glutamate release when Gaba synthesis is impaired, homeostatic mechanisms ensure that the RBC output operates within its normal range after eye opening, perhaps to regain proper visual processing within the scotopic pathway.
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distinct ionotropic Gaba receptors mediate presynaptic and postsynaptic inhibition in retinal bipolar cells
The Journal of Neuroscience, 2000Co-Authors: Colleen R Shields, My N Tran, Rachel O L Wong, Peter D LukasiewiczAbstract:Ionotropic Gaba receptors can mediate presynaptic and postsynaptic inhibition. We assessed the contributions of GabaA and GabaC receptors to inhibition at the dendrites and axon terminals of ferret retinal bipolar cells by recording currents evoked by focal application of Gaba in the retinal slice. Currents elicited at the dendrites were mediated predominantly by GabaA receptors, whereas responses evoked at the terminals had GabaA and GabaC components. The ratio of GabaC to GabaA(GabaC:GabaA) was highest in rod bipolar cell terminals and variable among cone bipolars, but generally was lower in OFF than in ON classes. Our results also suggest that the GabaC:GabaA could influence the time course of responses. Currents evoked at the terminals decayed slowly in cell types for which the GabaC:GabaA was high, but decayed relatively rapidly in cells for which this ratio was low. Immunohistochemical studies corroborated our physiological results. GabaA β2/3 subunit immunoreactivity was intense in the outer and inner plexiform layers (OPL and IPL, respectively). GabaC ρ subunit labeling was weak in the OPL but strong in the IPL in which puncta colocalized with terminals of rod bipolars immunoreactive for protein kinase C and of cone bipolars immunoreactive for calbindin or recoverin. These data demonstrate that GabaA receptors mediate Gabaergic inhibition on bipolar cell dendrites in the OPL, that GabaA and GabaCreceptors mediate inhibition on axon terminals in the IPL, and that the GabaC:GabaA on the terminals may tune the response characteristics of the bipolar cell.
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a novel Gaba receptor modulates synaptic transmission from bipolar to ganglion and amacrine cells in the tiger salamander retina
The Journal of Neuroscience, 1994Co-Authors: Peter D Lukasiewicz, F S WerblinAbstract:We investigated the mechanisms underlying the modulation of transmitter release from bipolar cells. Three currents, measured under whole-cell patch clamp in the tiger salamander retinal slice, were used to identify the sites of modulation and to establish their pharmacological profile. (1) A light-elicited inhibitory current was measured in bipolar cells that could be blocked by picrotoxin. This input probably arrives via Gabaergic amacrine cells since there is high Gaba sensitivity at the bipolar cell terminals and little Gaba sensitivity at the dendrites. (2) Voltage-gated barium currents were elicited by depolarizing voltage ramps in bipolar cells. These currents most likely flowed through the calcium channels that are associated with transmitter release at the bipolar terminal. Bath-applied Gaba suppressed the barium currents. (3) Puffs of potassium at bipolar dendrites depolarized bipolar cells and elicited an excitatory synaptic current measured in amacrine and ganglion cells. The excitatory synaptic currents, which reflect bipolar cell transmitter release, were also blocked by bath-applied Gaba. For all three currents, the effects of Gaba could be reversed by picrotoxin, but not by bicuculline or SR95531. The pharmacological profile of the receptors mediating Gaba suppression of the barium currents and of excitatory synaptic transmission is characteristic of GabaC receptors (Cutting et al., 1991; Polenzani et al., 1991; Shimada et al., 1992). Gaba receptors at bipolar terminals gate a chloride conductance, and most were found to have the pharmacological properties of GabaC receptors (Lukasiewicz et al., 1994). By contrast, the Gaba receptors on ganglion cells have been found to be the GabaA subtype (Lukasiewicz and Werblin, 1990; Lukasiewicz et al., 1994). These results suggest that Gaba acts presynaptically at GabaC receptors at the bipolar cell terminals. The GabaC receptors open chloride channels that can modulate the release of excitatory transmitter. In some experiments, bicuculline or SR95531 reversed a component of the Gaba suppression of synaptic transmission. This indicates that GabaA receptors may also play a role in modulating transmission between bipolar and ganglion cells.
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a novel Gaba receptor on bipolar cell terminals in the tiger salamander retina
The Journal of Neuroscience, 1994Co-Authors: Peter D Lukasiewicz, Bruce R. Maple, F S WerblinAbstract:We studied the pharmacology of the Gaba receptors on bipolar cell terminals in the retinal slice preparation. Whole-cell patch-clamp recordings were made from the somas of bipolar cells and Gaba was puffed near their terminals, after synaptic transmission was blocked. Gaba puffs evoked a large chloride current that was reduced by picrotoxin, but in many cells this current was insensitive to blockade by the competitive GabaA receptor antagonists bicuculline and SR95531. Pentobarbital, an enhancer of GabaA receptor-mediated responses, did not significantly increase the magnitude of the current responses to Gaba puffed at the bipolar cell terminals. To confirm the effectiveness of GabaA antagonists and pentobarbital in the slice preparation, we measured Gaba currents in ganglion cells. In contrast to bipolar cells, the ganglion cell Gaba responses were strongly reduced by both bicuculline and SR95531. In addition, pentobarbital strongly enhanced the action of Gaba at the ganglion cells. The isomeric Gaba agonists cis- and transaminocrotonic acid (CACA and TACA), elicited picrotoxin- sensitive currents in both bipolar and ganglion cells. TACA was more effective than CACA at both cell types. In bipolar cells, TACA and CACA currents were relatively resistant to bicuculline blockade, but in ganglion cells both currents were reduced by bicuculline. Gaba receptors on bipolar terminals appear to be pharmacologically different from the Gaba receptors found on ganglion cell dendrites. The bipolar cell terminal Gaba receptor pharmacology is similar to the pharmacology reported for the rho 1 Gaba receptor subunit that was isolated from retina and expressed in Xenopus oocytes (Cutting et al., 1991; Polenzani et al., 1991; Shimada et al., 1992). This receptor, which is both bicuculline and pentobarbital insensitive, has been called the GabaC receptor (Johnston, 1986; Shimada et al., 1992). However, some bipolar cells were somewhat sensitive to blockade by bicuculline, suggesting that these cells had both GabaA and GabaC receptors on their bipolar terminals.
L F Nurullin - One of the best experts on this subject based on the ideXlab platform.
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metabotropic Gabab receptors mediate Gaba inhibition of acetylcholine release in the rat neuromuscular junction
Journal of Neurochemistry, 2015Co-Authors: A I Malomouzh, Konstantin A Petrov, L F Nurullin, E E NikolskyAbstract:Gamma-aminobutyric acid (Gaba) is an amino acid which acts as a neurotransmitter in the central nervous system. Here, we studied the effects of Gaba on non-quantal, spontaneous, and evoked quantal acetylcholine (ACh) release from motor nerve endings. We found that while the application of 10 μM of Gaba had no effect on spontaneous quantal ACh release, as detected by the frequency of miniature endplate potentials, Gaba reduced the non-quantal ACh release by 57%, as determined by the H-effect value. Finally, the evoked quantal ACh release, estimated by calculating the quantal content of full-sized endplate potentials (EPPs), was reduced by 34%. Gaba's inhibitory effect remained unchanged after pre-incubation with picrotoxin, an ionotropic GabaA receptor blocker, but was attenuated following application of the GabaB receptor blocker CGP 55845, which itself had no effect on ACh release. An inhibitor of phospholipase C, U73122, completely prevented the Gaba-induced decrease in ACh release. Immunofluorescence demonstrated the presence of both subunits of the GabaB receptor (GabaB R1 and GabaB R2) in the neuromuscular junction. These findings suggest that metabotropic GabaB receptors are expressed in the mammalian neuromuscular synapse and their activation results in a phospholipase C-mediated reduction in the intensity of non-quantal and evoked quantal ACh release. We investigated the effect of gamma-aminobutyric acid (Gaba) on neuromuscular transmission. Gaba reduced the non-quantal and evoked quantal release of acetylcholine. These effects are mediated by GabaB receptors and are implemented via phospholipase C (PLC) activation. Our findings suggest that in the mammalian neuromuscular synapse, metabotropic GabaB receptors are expressed and their activation results in a reduction in the intensity of acetylcholine release.
A I Malomouzh - One of the best experts on this subject based on the ideXlab platform.
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metabotropic Gabab receptors mediate Gaba inhibition of acetylcholine release in the rat neuromuscular junction
Journal of Neurochemistry, 2015Co-Authors: A I Malomouzh, Konstantin A Petrov, L F Nurullin, E E NikolskyAbstract:Gamma-aminobutyric acid (Gaba) is an amino acid which acts as a neurotransmitter in the central nervous system. Here, we studied the effects of Gaba on non-quantal, spontaneous, and evoked quantal acetylcholine (ACh) release from motor nerve endings. We found that while the application of 10 μM of Gaba had no effect on spontaneous quantal ACh release, as detected by the frequency of miniature endplate potentials, Gaba reduced the non-quantal ACh release by 57%, as determined by the H-effect value. Finally, the evoked quantal ACh release, estimated by calculating the quantal content of full-sized endplate potentials (EPPs), was reduced by 34%. Gaba's inhibitory effect remained unchanged after pre-incubation with picrotoxin, an ionotropic GabaA receptor blocker, but was attenuated following application of the GabaB receptor blocker CGP 55845, which itself had no effect on ACh release. An inhibitor of phospholipase C, U73122, completely prevented the Gaba-induced decrease in ACh release. Immunofluorescence demonstrated the presence of both subunits of the GabaB receptor (GabaB R1 and GabaB R2) in the neuromuscular junction. These findings suggest that metabotropic GabaB receptors are expressed in the mammalian neuromuscular synapse and their activation results in a phospholipase C-mediated reduction in the intensity of non-quantal and evoked quantal ACh release. We investigated the effect of gamma-aminobutyric acid (Gaba) on neuromuscular transmission. Gaba reduced the non-quantal and evoked quantal release of acetylcholine. These effects are mediated by GabaB receptors and are implemented via phospholipase C (PLC) activation. Our findings suggest that in the mammalian neuromuscular synapse, metabotropic GabaB receptors are expressed and their activation results in a reduction in the intensity of acetylcholine release.
Ei Terasawa - One of the best experts on this subject based on the ideXlab platform.
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gamma aminobutyric acid is an inhibitory neurotransmitter restricting the release of luteinizing hormone releasing hormone before the onset of puberty
Proceedings of the National Academy of Sciences of the United States of America, 1994Co-Authors: Dai Mitsushima, David L Hei, Ei TerasawaAbstract:To test the hypothesis that the pubertal increase in luteinizing hormone-releasing hormone (LHRH) release is withheld by a dominant inhibitory neuronal system, the role of gamma-aminobutyric acid (Gaba), a known inhibitory neurotransmitter, in the control of LHRH release was examined in conscious female monkeys at the prepubertal and pubertal stages using a push-pull perfusion method. Gaba, bicuculline (a GabaA receptor blocker), and 2-hydroxysaclofen (a GabaB receptor blocker) were directly infused into the stalk-median eminence while perfusates were collected for LHRH determination. Bicuculline, but not saclofen, induced a large and prompt increase in LHRH release in prepubertal monkeys, whereas it stimulated LHRH release slightly in pubertal monkeys. In contrast, Gaba suppressed LHRH release in pubertal, but not prepubertal, monkeys. These differential effects of Gaba and the Gaba antagonist on LHRH release in the two developmental stages were due to an age factor rather than to the steroid hormonal background. Moreover, Gaba release in the stalk-median eminence of prepubertal monkeys was much higher than that in pubertal monkeys. Thus, the results suggest that in the prepubertal period there is a powerful Gaba inhibition of the LHRH neurosecretory system: infusions of GabaA, but not GabaB, antagonists stimulate LHRH release by removal of the endogenous Gaba inhibition, whereas exogenous Gaba is ineffective because of high endogenous Gaba levels. The decrease of this tonic inhibition may be a key factor for the onset of puberty in non-human primates.
